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  • 1. Bagge, Louise
    et al.
    Probst, Johan
    Jensen, Steen M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Blomström, Per
    Thelin, Stefan
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Blomström-Lundqvist, Carina
    Quality of life is not improved aftermitral valve surgery combined with epicardial left atrial cryoablation as compared with mitral valve surgery alone: a substudy of the double blind randomized SWEDish Multicentre Atrial Fibrillation study (SWEDMAF)2018In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 20, p. F343-F350Article in journal (Refereed)
    Abstract [en]

    Aims: Concomitant surgical ablation of atrial fibrillation (AF) in patients undergoing mitral valve surgery (MVS) has almost become routine despite lack of convincing information about improved quality-of-life (QOL) and clinical benefit. Quality-of-life was therefore assessed after MVS with or without epicardial left atrial cryoablation. Methods and results: Sixty-five patients with permanent AF randomized to MVS with or without left atrial cryoablation, in the doubleblinded multicentre SWEDMAF trial, replied to the Short Form 36 QOL survey at 6 and 12 months follow-up. The QOL scores at 12month follow-up did not differ significantly between patients undergoing MVS combined with cryoablation vs. those undergoing MVS alone regarding Physical Component Summary mean 42.8 (95% confidence interval 38.3-47.3) vs. mean 44.0 (40.1-47.7), P =0.700 or Mental Component Summary mean 53.1 (49.7-56.4) vs. mean 48.4 (44.6-52.2), P=0.075. All patients, irrespective of allocated procedure, reached the same QOL after surgery as an age-matched Swedish general population. The Physical Component Summary in patients with sinus rhythm did also not differ from those in AF at 12months; mean 45.4 (42.0-48.7) vs. mean 40.5 (35.5-45.6), P=0.096) nor was there a difference in Mental Component Summary; mean 51.0 (48.0-54.1) vs. mean 49.6 (44.6-54.5), P=0.581). Conclusion: Left atrial cryoablation added to MVS does not improve health-related QOL in patients with permanent AF, a finding that raises concerns regarding recommendations made for this combined procedure.

  • 2.
    Calcutteea, Avin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Organised right ventricular remodelling in aortic stenosis even after valve replacement2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 2, p. 1549-1550Article in journal (Refereed)
  • 3.
    Ding, Wenhong
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zhao, Ying
    Watt, Astrid
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nilsson, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Weintar, Reidar
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ruck, Andreas
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Early effect of TAVI on left ventricular function in severe aortic stenosis: trans-apical vs. trans-femoral approachManuscript (preprint) (Other academic)
  • 4.
    Henein, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmner, Fredrik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Long anterior mitral leaflet causing outflow tract obstruction in a symptomatic patient with hypertrophic cardiomyopathy: the role of mitral valve surgical correction2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 204, p. 86-87Article in journal (Refereed)
  • 5.
    Henein, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hällgren, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sörensen, Karen
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Kofoed, Klaus Fuglsang
    Larsen, Linnea Hornbech
    Hassager, Christian
    Aortic root, not valve, calcification correlates with coronary artery calcification in patients with severe aortic stenosis: a two-center study2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 243, no 2, p. 631-637Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The underlying pathology in aortic stenosis (AS) and coronary artery stenosis (CAS) is similar including atherosclerosis and calcification. We hypothesize that coronary artery calcification (CAC) is likely to correlate with aortic root calcification (ARC) rather than with aortic valve calcification (AVC), due to tissue similarity between the two types of vessel rather than with the valve leaflet tissue.

    MATERIAL AND METHODS: We studied 212 consecutive patients (age 72.5 ± 7.9 years, 91 females) with AS requiring aortic valve replacement (AVR) in two Heart Centers, who underwent multidetector cardiac CT preoperatively. CAC, AVC and ARC were quantified using Agatston scoring. Correlations were tested by Spearman's test and Mann-Whitney U-test was used for comparing different subgroups; bicuspid (BAV) vs tricuspid (TAV) aortic valve.

    RESULTS: CAC was present in 92%, AVC in 100% and ARC in 82% of patients. CAC correlated with ARC (rho = 0.51, p < 0.001) but not with AVC. The number of calcified coronary arteries correlated with ARC (rho = 0.45, p < 0.001) but not with AVC. 29/152 patients had echocardiographic evidence of BAV and 123 TAV, who were older (p < 0.001) but CAC was associated with TAV even after adjusting for age (p = 0.01). AVC score was associated with BAV after adjusting for age (p = 0.03) but ARC was not. Of the total cohort, 82 patients (39%) had significant coronary stenosis (>50%), but these were not different in the pattern of calcification from those without CAS. CAC was consistently higher in patients with risk factors for atherosclerosis compared to those without.

    CONCLUSION: The observed relationship between coronary and aortic root calcification suggests a diffuse arterial disease. The lack of relationship between coronary and aortic valve calcification suggests a different pathology.

  • 6.
    Henein, Michael Y
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Left atrial function in volume versus pressure overloaded left atrium2015In: The International Journal of Cardiovascular Imaging, ISSN 1569-5794, E-ISSN 1875-8312, Vol. 31, no 5, p. 959-965Article in journal (Refereed)
    Abstract [en]

    Left atrial (LA) pressure and volume overload both result in cavity enlargement and complications. LA volume has been shown to predict such complications, but it does not reflect myocardial function, which can be accurately assessed using myocardial deformation measurements. We hypothesized that volume overloaded LA have maintained myocardial function compared to pressure overloaded ones. We tested this hypothesis in 44 patient (mean age 62 ± 12 years) with LA volume overload (LAVOL) due to severe mitral regurgitation (MR) with no indirect signs of elevated left ventricular (LV) filling pressures based on Doppler measured isovolumic relaxation time >60 ms. We compared them with 24 (mean age 64 ± 12 years) patient with LA pressure overload (LAPOL) who proved to have PCWP >15 mmHg on right heart catheterization. Twenty-seven healthy controls (mean age 57 ± 10 years) constituted a control group. Patients with LAVOL had larger LA volumes, higher LV ejection fraction, global LV strain (LVGLS) and transmitral and pulmonary veins flow velocities (p < 0.05) and better LA atrial strain rate (LASR) function compared to LAPOL (p < 0.001). In LAVOL, the LASR during atrial contraction (LASRa) was lower than in controls (p < 0.05) indicating LA mechanical disturbances. LVGLS correlated with peak atrial longitudinal systolic strain in the whole group (r = -0.65, p < 0.001) and less so with LASRa (r = -0.43, p < 0.001) Conclusion: Irrespective of a smaller LA volume, LAVOL had less negative effect on LA myocardial function than LAPOL. Thus, monitoring atrial myocardial contraction might be useful in following patients with significant MR.

  • 7.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Metabolic risk markers and relative survival in patients with aortic stenosis requiring surgery2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Aortic stenosis (AS) is the most common valve disorder requiring surgery in developed countries. The etiology of AS is only partly known.  Identification of new biomarkers in prospective studies could lead to novel insights in the etiology of AS, and possibly lead to improved clinical management. Long term observed survival after aortic valve surgery has improved over the last decades despite an ageing population presenting with more comorbidities. Whether this is reflected in improved relative survival is not known. We evaluated if biomarkers associated prospectively with AS requiring surgery, and if these associations differed between genders, time to surgery and the presence of coronary artery disease (CAD). We also assessed long term observed and relative survival after aortic valve surgery with and without concomitant coronary artery by-pass surgery (CABG).

    Methods and results: Study I: We prospectively studied the impact of lipoprotein (a)(Lp[a]) and apolipoproteins (Apo) in subgroups of AS. During a 20-year period, 336 patients with prior participation in large population-based surveys in northern Sweden were operated due to AS plus CABG when indicated. For each case two referents were matched. Data from the baseline survey were collected and included data on cardiovascular risk factors, health history, measurements of anthropometry, blood pressure, blood glucose and blood lipid levels were retrieved. Data from pre- and perioperative assessments were also collected. The presence of CAD was determined from the coronary angiogram. Elevated levels of Lp(a) and an elevated Apo B/Apo A 1 ratio were independently associated with future surgery for AS, but only in patients with concomitant CAD (OR 1.29, 95 % CI 1.07-1.55 and 1.43, 95 % CI 1.16-1.76 respectively). Study II: The same patient cohort as in study I was used. A panel of 92 cardiovascular candidate proteins were analysed with the multiplex proximity extension assay in samples obtained at baseline. Six circulating proteins (growth differentiation factor 15[GDF-15], galectin-4, von Willebrand factor [vWF], interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9, [PCSK9]) were associated with future surgery for AS in patients with concurrent CAD (ORs ranged from 1.25 to 1.37 per SD increase in the protein signal). In the validation study with 106 additional cases, the association of all but one, (interleukin 17 receptor A), of these proteins were replicated in patients with AS and concurrent CAD but not in those without concurrent CAD. Study III: In the same patient cohort as in study I and II we evaluated if troponin T (TnT) and C-reactive protein (CRP) associated prospectively with future surgery for AS. TnT was independently associated with surgery for AS in patients both with (OR 1.22, 95 % CI 1.02-1.46) and without concomitant CAD (1.39, 95% CI 1.05-1.84). CRP was not associated with surgery for AS (OR 1.06, 95 % CI 0.92-1.23). Study IV: 4970 patients between 2005 and 2016 from three Swedish heart surgery centres, undergoing aortic valve replacement (AVR) due to either AS or aortic regurgitation in conjunction with CABG when indicated, were followed up. All-cause mortality, as well as both observed and relative survival, was analysed with focus on age, sex, type of valve prosthesis and the impact of concomitant CABG. Median follow-up was 4.7 years (2.3-7.6). 30-day mortality was 2.3 %. Long-term survival with 30-day mortality excluded was 96.6 %, 82.7 %, 57.6 % after 1, 5 and 10 years respectively. Relative survival rates (adjusting for the background mortality in the general Swedish population based on age, sex and year) were 99.6 %, 99.5 % and 90.6 % after 1, 5 and 10 years respectively. Age had a negative influence on observed survival (p<0.001) but was associated with better relative survival (relative mortality rate [RMR] 0.74, 95 % CI 0.71 - 0.77). Women had a lower observed mortality than men (p<0.001) but a lower relative survival (RMR 1.17, 95 % CI 1.02-1.35). Combined surgery (AVR+CABG) was not significantly associated with higher mortality (p=0.43) in a multivariable adjusted analysis. The presence of bicuspid morphology was associated with lower observed mortality compared with tricuspid valve, and a relative survival matching that in the general population.

    Conclusion: I. Plasma levels of Lp(a) and the Apo B/Apo A 1 ratio were independently associated with future surgery for AS but only in patients with concomitant CAD. This finding suggests that patients with AS have different phenotypes and may open a new avenue of research on targeted risk factor interventions in this population. II. Five circulating proteins – GDF-15, galectin-4, vWF, transferrin receptor protein 1, and PCSK9 – were associated with the need for aortic valve surgery several years later. The role of these proteins should be investigated in future studies. III. Elevated plasma levels of TnT were independently associated with future surgery for AS, irrespective of the presence of concomitant CAD, which could indicate that the myocardium is subject to mechanical stress already in the subclinical stage of AS. This may be used as a clinical tool for identification of patients with subclinical AS who could benefit from early intervention. Elevated CRP levels did not associate with future AVR. IV. Relative survival following AVR was particularly good in the elderly matching that in the general population underlining the benefits of aortic valve surgery in properly selected patients. Women had decreased relative survival compared to men. This should be explored in future studies. Adding CABG to an AVR procedure was not associated with increased risk. Bicuspid valve morphology was associated with lower observed mortality compared with tricuspid valve morphology, and with a relative survival matching that of the general population.

  • 8.
    Holmgren, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bull Enger, Tone
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Videm, Vibeke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Valle, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Dybvad Evjemo, Karen Julie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wahba, Alexander
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Results of surgical aortic valve replacement in a Swedish population: relative survival vs. observed mortalityManuscript (preprint) (Other academic)
  • 9.
    Holmgren, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ljungberg, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    TroponinT but not C-reactive protein is associated with future surgery for aortic stenosis - a population based nested case-refeent study.Manuscript (preprint) (Other academic)
  • 10.
    Holmgren, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Rumsby, Gill
    Gustafsson, Sandra
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The nature of cardiac calcification in aortic stenosis2012In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 158, no 2, p. 319-321Article in journal (Refereed)
  • 11.
    Ljungberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lipoprotein(a) and the Apolipoprotein B/A1 Ratio Independently Associate With Surgery for Aortic Stenosis Only in Patients With Concomitant Coronary Artery Disease2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e007160Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Aortic stenosis (AS) has different clinical phenotypes, including AS with or without concomitant coronary artery disease (CAD). It is unknown whether these phenotypes share the same risk factors. In particular, lipoprotein(a) [Lp(a)] and apolipoproteins (Apo) are associated with AS, but it is unknown whether these associations differ among phenotypes. In this prospective analysis we examined the impact of Lp(a) and Apo in subgroups of patients with AS.

    METHODS AND RESULTS: We identified 336 patients (mean age at survey 56.7 years, 48% female) who underwent surgery for AS after a median 10.9 years (interquartile range 9.3 years), participants in 1 of 3 large population surveys. For each patient, 2 matched referents were allocated. Lp(a) and Apo were analyzed in the baseline samples. Uni- and multivariable logistic regression analyses were used to estimate risks related to a 1 (ln) standard deviation increase in Lp(a) and the ratio of Apo B to Apo A1 (Apo B/A1 ratio). High levels of Lp(a) predicted surgery for AS in 203 patients with concomitant CAD (odds ratio [95% confidence intervals]) (1.29 [1.07-1.55]), but not in 132 patients without CAD (1.04 [0.83-1.29]) in the fully adjusted model. Similarly, a high Apo B/A1 ratio predicted surgery in patients with concomitant CAD (1.43 [1.16-1.76]) but not in those without CAD (0.87 [0.69-1.10]).

    CONCLUSIONS: High levels of Lp(a) and a high Apo B/A1 ratio were associated with surgery for AS in patients with concomitant CAD but not in those with isolated AS. This finding may lead to a new avenue of research for targeted risk factor interventions in this population.

  • 12.
    Ljungberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Janiec, Mikael
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Siegbahn, Agneta
    Fall, Tove
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, no 6Article in journal (Refereed)
    Abstract [en]

    Background: Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights. Methods: Within a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study. Results: Six proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease. Conclusions: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.

  • 13.
    Ljungberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, no 7, p. 524-530Article in journal (Refereed)
    Abstract [en]

    Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR(cystatin C) and eGFR(creatinine) and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR(cystatin C) and eGFR(creatinine). A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73-0.97]), especially in women (0.74 [0.60-0.92] vs. 0.93 [0.76-1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44-0.83] and 0.89 [0.65-1.23], respectively). In conclusion, a high ratio between eGFR(cystatin C) and eGFR(creatinine) was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.

  • 14.
    Ljungberg, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Early impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosisManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction 

    Renal insufficiency is a known risk factor for cardiovascular disease. However, it is unknown if early impairment in renal function is associated with increased risk for aortic stenosis (AS). Recently a new approach was proposed to detect early impairment in renal function by using the ratio between glomerular filtration rate (GFR) calculated by cystatin C and GFR calculated by creatinine. 

    Purpose 

    To evaluate if the ratio between GFR cystatin C and GFR creatinine is associated with increased risk for AS requiring surgery and further, to evaluate if the ratio associates with survival. 

    Methods 

    We identified 334 patients that underwent surgery for AS after participation in population surveys (median age (interquartile range) 59.4 (10.3) years at survey and 68.3 (12.7) at surgery, 48% females). For each patient, two matched referents were allocated. Circulating levels of cystatin C and creatinine were determined at baseline (survey). Estimated glomerular filtration rates (eGFR) were calculated using the CAPA and Lund-Malmö-Revised formulas. Uni- and multivariable conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval]) related to one (ln) standard deviation increase in cystatin C, creatinine, eGFR cystatin C, eGFR creatinine, and in the ratio between eGFR cystatin C and eGFR creatinine, respectively. 

    Results 

    A high ratio was associated with lower risk for AS requiring surgery (OR 0.84 [0.73–0.97]). After stratification for sex, this effect was seen in women but not in men (0.74 [0.60–0.92] and 0.93 [0.76 [0.76–1.13], respectively). After further stratification for CAD, the association remained in women with CAD, but the effect was not seen in men with CAD (0.60 [0.44–0.83] and 0.96 [0.76 [0.75–1.23]). A high ratio was associated with longer survival in the entire cohort (HR 0.84 [0.75–0.95]). 

    Conclusion 

    A high ratio between eGFR based on cystatin C and eGFR based on creatinine was associated with lower risk for surgery for AS in those with CAD with a clear sex-difference. Early renal impairment is thus associated with future risk for AS requiring surgery. Further, a high ratio relates to longer survival. 

  • 15.
    Ramzy, Ihab S
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Gustafsson, Sandra
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Early effect of surgical revascularisation on left ventricular twist function2015In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 4, p. 16-23Article in journal (Refereed)
  • 16.
    Svenmarker, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Serum markers are not reliable measures of renal function in conjunction with cardiopulmonary bypass2011In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 12, no 5, p. 713-717Article in journal (Refereed)
    Abstract [en]

    The present study explored the influence of haemodilution on estimates of the glomerular filtration rate (GFR) in conjunction with cardiopulmonary bypass (CPB) and cardiac surgery. Ninety-eight patients (n = 98) undergoing coronary artery bypass grafting with the aid of CPB were examined. The serum concentration of cystatin C and creatinine was analysed prior to surgery, after completion of CPB and in the intensive care the day after surgery. The estimated GFR was calculated using standard equations based on the serum concentration of cystatin C and creatinine. It was found that haemodilution induced by CPB had significant effects on the estimated GFR. For cystatin C, the GFR increased by 50.5 ± 2.5 ml/min (P = 0.000) and for creatinine based GFR with 22.5 ± 0.9 ml/min (P = 0.000) using the 4-variable modification of diet renal disease formula and with 22.1 ± 0.93 ml/min (P = 0.000) for the Cockcroft-Gault formula, respectively. Similar effects of haemodilution on GFR were also detected postoperatively. Haemodilution induced by CPB may therefore significantly overestimate the renal function as indicated by GFR based on serum markers.

  • 17. Vanoli, Davide
    et al.
    Backman, Christer
    Holmgren, Anders
    Inferior infarction complicated by ruptured interventricular septum2015In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 2, no 1, p. 44-45Article in journal (Refereed)
  • 18. Vorkas, P. A.
    et al.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Want, E. J.
    Issac, G.
    Millar, A.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. ulf.naslund@medicin.umu.se.
    Holmes, E.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Apoptosis is a potential mechanism for severe calcific coronary artery disease2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P2550, p. 456-456Article in journal (Other academic)
  • 19.
    Vorkas, P.
    et al.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Want, E.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Holmes, E.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. ulf.naslund@medicin.umu.se.
    Issac, G.
    Corporation, Waters Corporation, Milford, USA.
    Millar, A.
    Corporation, Waters Corporation, Milford, USA.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Apoptosis is a potential mechanism for severe calcific coronary artery disease2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E157-E158Article in journal (Other academic)
  • 20.
    Vorkas, P.
    et al.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Want, E.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Holmes, E.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. ulf.naslund@medicin.umu.se.
    Issac, G
    Corporation, Waters Corporation, Milford, USA.
    Millar, A
    Corporation, Waters Corporation, Milford, USA.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Significant inflammation pathophysiology features calcific coronary artery disease2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E140-E140Article in journal (Other academic)
  • 21. Vorkas, Panagiotis A.
    et al.
    Isaac, Giorgis
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Want, Elizabeth J.
    Shockcor, John P.
    Holmes, Elaine
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Perturbations in fatty acid metabolism and apoptosis are manifested in calcific coronary artery disease: An exploratory lipidomic study2015In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 197, p. 192-199Article in journal (Refereed)
    Abstract [en]

    Background: Controversy exists concerning the beneficial or harmful effects of the presence of ectopic calcification in the coronary arteries. Additionally, further elucidation of the exact pathophysiological mechanism is needed. In this study, we sought to identify metabolic markers of vascular calcification that could assist in understanding the disease, monitoring its progress and generating hypotheses describing its pathophysiology. Methods: Untargeted lipid profiling and complementary modeling strategies were employed to compare serum samples from patients with different levels of calcific coronary artery disease (CCAD) based on their calcium score (CS). Subsequently, patients were divided into three groups: no calcification (NC; CS = 0; n = 26), mild calcification (MC; CS: 1-250; n = 27) and severe (SC; CS > 250; n = 17). Results: Phosphatidylcholine levels were found to be significantly altered in the disease states (p = 0.001-0.04). Specifically, 18-carbon fatty acyl chain (FAC) phosphatidylcholines were detected in lower levels in the SC group, while 20:4 FAC lipid species were detected in higher concentrations. A statistical trend was observed with phosphatidylcholine lipids in the MC group, showing the same tendency as with the SC group. We also observed several sphingomyelin signals present at lower intensities in SC when compared with NC or MC groups (p = 0.000001-0.01). Conclusions: This is the first lipid profiling study reported in CCAD. Our data demonstrate dysregulations of phosphatidylcholine lipid species, which suggest perturbations in fatty acid elongation/desaturation. The altered levels of the 18-carbon and 20:4 FAC lipids may be indicative of disturbed inflammation homeostasis. The marked sphingomyelin dysregulation in SC is consistent with profound apoptosis as a potential mechanism of CCAD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 22. Watt, A.
    et al.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Jashari, Haki
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Pre-operative right ventricular function predicts clinical outcome after prophylactic tricuspid ring implantation2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, p. 1107-1108Article in journal (Other academic)
  • 23.
    Zhao, Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Gustavsson, Sandra
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Residual compromised myocardial contractile reserve after valve replacement for aortic stenosis2012In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 13, no 4, p. 353-360Article in journal (Refereed)
    Abstract [en]

    Objective: Despite recovery of left ventricular (LV) function and morphology after aortic valve replacement (AVR) for aortic stenosis (AS), its relationship with exercise capacity remains unknown. Twenty-one AVR patients (age 61 +/- 12 years, 14 male) with normal ejection fraction (EF, 64 +/- 7%) and 21 age- and sex-matched controls (57 +/- 9 years, 10 male, EF 68 +/- 8%) were studied.Methods and results: All subjects performed semi-supine bicycle exercise and speckle tracking echocardiography (STE) study. Peak oxygen consumption (pVO(2)) was collected during semi-supine bicycle exercise. Systolic (GLSRs) and early diastolic (GLSRe) longitudinal strain rate using STE and Doppler echocardiographic parameters were measured at rest, submaximal, peak exercise, and 4 min after exercise. The two groups had comparable resting echocardiographic measurements. At peak exercise, pVO(2) was lower in patients than controls (18.5 +/- 4.5 vs. 22.1 +/- 4.3 L/min/kg, P < 0.05). GLSRs (0.98 +/- 0.28 vs. 1.55 +/- 0.30 1/s, P < 0.001), septal Sm (7.9 +/- 1.4 vs. 11.1 +/- 2.3 cm/s, P < 0.001) and their changes between rest and peak exercise (Delta GLSRs: 0.16 +/- 0.33 vs. 0.68 +/- 0.27 1/s, P < 0.001; Delta Sm 2.29 +/- 2.23 vs. 4.63 +/- 2.29 cm/s, P < 0.01) were significantly lower in patients than controls. There was no correlation between pVO(2) and any echocardiographic measurements in controls. In patients, pVO(2) correlated with peak exercise GLSRs (r = 0.60, P = 0.0007), septal Sm (r = 0.65, P = 0.002), and Em (r = 0.57, P = 0.009). In a multivariate model, peak exercise GLSRs (beta = 7.18, P = 0.03) was the only independent predictor of pVO(2) in the patients group.Conclusion: Exercise capacity is subnormal after AVR for AS, irrespective of normal LVEF suggesting residual compromised myocardial functional reserve.

  • 24.
    Zhao, Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nilsson, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Trans-catheter aortic valve implantation: early recovery of left and preservation of right ventricular function2011In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 12, no 1, p. 35-39Article in journal (Refereed)
    Abstract [en]

    This study aimed to assess the early effect of trans-catheter aortic valve implantation (TAVI) on right (RV) and left ventricular (LV) function in severe aortic stenosis (AS) patients. Twenty AS patients (age 79±6 years) were examined before, one week and six weeks after TAVI using Doppler echocardiography. LV ejection fraction (EF), long-axis [mitral annular plane systolic excursion (MAPSE)] and RV long-axis [tricuspid annular plane systolic excursion (TAPSE)] function, septal radial motion were studied. Results were compared with 30 AS patients before and one week after aortic valve replacement (AVR) as well as 30 normals (reference group). Before TAVI, LVEF was reduced and E/A was higher than the reference and AVR groups (P<0.05 for all). MAPSE, TAPSE and septal motion were equally reduced in TAVI and AVR patients (P<0.05 for all). One week after the TAVI, EF increased in patients with values <50% before the procedure. In contrast, AVR resulted in reversed septal motion (P<0.001) and depressed TAPSE (P<0.001). The extent of reversed septal motion correlated with that of TAPSE in the patients group as a whole after procedures (r=0.78, P<0.001). Six weeks after TAVI, RV function remained unchanged, but LVEF increased and E/A decreased (P<0.05 for both). Thus, TAVI procedure results in significant early improvement of LV systolic and diastolic function particularly in patients with reduced EF and preserves RV systolic function.

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